Relationships between the islets blood flow, nitric oxide, insulin, and cytosolic calcium in rat pancreatic islets: effects of DPP-IV inhibitor vildagliptin.

The aim of the present study was to evaluate the relationships between the islets blood flow, nitric oxide, insulin, and cytosolic calcium in rat pancreatic islets, using dipeptidyl peptidase-IV (DPP-IV) inhibitor vildagliptin. For measuring pancreatic and islets blood a non-radioactive microsphere technique was used. Vehicle pre-treatment of glucose administered diabetic rats had decrease pancreatic and islets blood flow as compared with glucose administered normal rats. Blood glucose concentrations were not affected after vildagliptin administration in either diabetic or normal rats (10 min after glucose administration). Vildagliptin had no effects on baseline pancreatic or islets blood flow in glucose administered normal rats. Administration of vildagliptin increased both pancreatic and islets blood flow as compared with vehicle treated diabetic rats. Furthermore, diabetic rats showed significant increase in NO and decrease in insulin secretions and vice versa in normal rats. Vildagliptin pre-treatment to both normal and diabetic rats had shown mild decrease in NO, but significantly increased insulin secretions. In addition, vildagliptin itself is able to mobilize intracellular Ca(2+) in pancreatic islets both in absence and presence of glucose. From the present study, we conclude following points (A) administration of vildagliptin augmented the blood flow seen in islets of diabetic rats, (B) islets insulin secretions are independent of islets blood flow and NO, (C) vildagliptin inhibited excessive NO production in diabetic rats that prevents the damage to β-cells due to excessive production of peroxynitrite (ONOO(-)) ions and protects from cytokine-induced suppression of insulin release.